Large animal models for cardiac remuscularization studies: A methodological review

Area of Science:

• Cardiovascular Research
• Regenerative Medicine
• Stem Cell Therapy

Background:

• Myocardial infarction (MI) is a leading cause of heart failure and mortality.
• Regenerating dead heart tissue with functional cardiomyocytes offers a potential therapeutic strategy.
• Human pluripotent stem cell-derived cardiomyocytes show promise for cardiac repair.

Purpose of the Study:

• To review large animal models for testing cardiomyocyte therapy in myocardial infarction.
• To assess the translatability of preclinical findings to clinical practice.
• To discuss methodologies for simulating human MI pathophysiology in animal models.

Main Methods:

• Focus on large mammal models simulating human myocardial infarction.
• Discussion of MI induction methodologies and animal species selection.
• Review of perioperative care, immunosuppression for xenotransplantation, cell source, and delivery.

Main Results:

• Large animal models are essential for rigorous safety and efficacy testing of stem cell-based cardiac remuscularization.
• Preclinical studies in large mammals increase the likelihood of successful clinical translation.
• Various aspects of model development and therapeutic delivery are critical for success.

Conclusions:

• Large animal models are indispensable for advancing cardiomyocyte therapy for myocardial infarction.
• Standardized methodologies in these models are key for reliable preclinical data.
• This review provides a framework for future research in cardiac regenerative medicine.